Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent manner
Abstract There is great interest on medium chain fatty acids (MCFA) for cardiovascular health. We explored the effects of MCFA on the expression of lipid metabolism and inflammatory genes in macrophages, and the extent to which they were mediated by the nuclear receptor peroxisome proliferator-activ...
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38700-x |
| _version_ | 1797774244913872896 |
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| author | Paula V. Gaete Luz D. Nieves-Barreto Valentina Guatibonza-García Mónica Losada-Barragán Karina Vargas-Sánchez Carlos O. Mendivil |
| author_facet | Paula V. Gaete Luz D. Nieves-Barreto Valentina Guatibonza-García Mónica Losada-Barragán Karina Vargas-Sánchez Carlos O. Mendivil |
| author_sort | Paula V. Gaete |
| collection | DOAJ |
| description | Abstract There is great interest on medium chain fatty acids (MCFA) for cardiovascular health. We explored the effects of MCFA on the expression of lipid metabolism and inflammatory genes in macrophages, and the extent to which they were mediated by the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR β/δ). J774A.1 murine macrophages were exposed to octanoate or decanoate as MCFA, a long-chain fatty acid control (palmitate), or the PPAR β/δ agonist GW501516, with or without lipopolysaccharide (LPS) stimulation, and with or without an siRNA-induced knockdown of PPAR β/δ. MCFA increased the expression of Plin2, encoding a lipid-droplet associated protein with anti-inflammatory effects in macrophages, in a partially PPAR β/δ-dependent manner. Both MCFA stimulated expression of the cholesterol efflux pump ABCA1, more pronouncedly under LPS stimulation and in the absence of PPAR β/δ. Octanoate stimulated the expression of Pltp, encoding a phospholipid transfer protein that aids ABCA1 in cellular lipid efflux. Only palmitate increased expression of the proinflammatory genes Il6, Tnf, Nos2 and Mmp9. Non-stimulated macrophages exposed to MCFA showed less internalization of fluorescently labeled lipoproteins. MCFA influenced the transcriptional responses of macrophages favoring cholesterol efflux and a less inflammatory response compared to palmitate. These effects were partially mediated by PPAR β/δ. |
| first_indexed | 2024-03-12T22:17:12Z |
| format | Article |
| id | doaj.art-c36a0524e4d544d9b7d8a21b2bd15281 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T22:17:12Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c36a0524e4d544d9b7d8a21b2bd152812023-07-23T11:14:40ZengNature PortfolioScientific Reports2045-23222023-07-0113111310.1038/s41598-023-38700-xMedium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent mannerPaula V. Gaete0Luz D. Nieves-Barreto1Valentina Guatibonza-García2Mónica Losada-Barragán3Karina Vargas-Sánchez4Carlos O. Mendivil5Department of Physiological Sciences, Universidad Nacional de ColombiaSchool of Medicine, Universidad de los AndesSchool of Medicine, Universidad de los AndesBiología Celular y Funcional e Ingeniería de Moléculas, Departamento de Biología, Universidad Antonio NariñoSchool of Medicine, Universidad de los AndesSchool of Medicine, Universidad de los AndesAbstract There is great interest on medium chain fatty acids (MCFA) for cardiovascular health. We explored the effects of MCFA on the expression of lipid metabolism and inflammatory genes in macrophages, and the extent to which they were mediated by the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR β/δ). J774A.1 murine macrophages were exposed to octanoate or decanoate as MCFA, a long-chain fatty acid control (palmitate), or the PPAR β/δ agonist GW501516, with or without lipopolysaccharide (LPS) stimulation, and with or without an siRNA-induced knockdown of PPAR β/δ. MCFA increased the expression of Plin2, encoding a lipid-droplet associated protein with anti-inflammatory effects in macrophages, in a partially PPAR β/δ-dependent manner. Both MCFA stimulated expression of the cholesterol efflux pump ABCA1, more pronouncedly under LPS stimulation and in the absence of PPAR β/δ. Octanoate stimulated the expression of Pltp, encoding a phospholipid transfer protein that aids ABCA1 in cellular lipid efflux. Only palmitate increased expression of the proinflammatory genes Il6, Tnf, Nos2 and Mmp9. Non-stimulated macrophages exposed to MCFA showed less internalization of fluorescently labeled lipoproteins. MCFA influenced the transcriptional responses of macrophages favoring cholesterol efflux and a less inflammatory response compared to palmitate. These effects were partially mediated by PPAR β/δ.https://doi.org/10.1038/s41598-023-38700-x |
| spellingShingle | Paula V. Gaete Luz D. Nieves-Barreto Valentina Guatibonza-García Mónica Losada-Barragán Karina Vargas-Sánchez Carlos O. Mendivil Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent manner Scientific Reports |
| title | Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent manner |
| title_full | Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent manner |
| title_fullStr | Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent manner |
| title_full_unstemmed | Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent manner |
| title_short | Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent manner |
| title_sort | medium chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a ppar β δ dependent manner |
| url | https://doi.org/10.1038/s41598-023-38700-x |
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